Neurodegenerative diseases such as Parkinson's disease and other alpha-synucleinopathies are chronic debilitating disorders for which no cure is known.
Parkinson's disease (PD) is a common neurodegenerative disorder that affects 1% of the population over 65. It is characterized by disabling motor abnormalities including tremor, slow movements, rigidity and poor balance. These impairments stem from the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Eventually, large percentages of patients develop dementia and hallucinations when the pathology involves other brain regions as well. Although the majority of Parkinson cases appear to be sporadic, the disorder runs in families in about 15-20% of the cases. To date, five distinct genes have been identified to cause PD including α-synuclein, parkin, dj-1, pink1 and lrrk2 1. Understanding how mutations in these genes cause neurodegeneration is crucial in the development of new treatments that might slow or stop the disease progression. Thus there remains a need for new treatments for the disease progression and for assays to help identify agents for such treatment.
Accumulating evidence indicates that increased levels of the protein α-synuclein is deleterious to neurons and can lead to such disorders including Parkinson's disease. This invention relates to the identification of a new mechanism by which the expression of this protein can be down-regulated by targeting its RNA. The study of and control of this heretofore unrecognized mechanism can be used as a therapeutic target and to screen small molecules that can mimic the effect for therapeutic intent in these diseases.